Succinhydrazides



Patented May 26, 1953 2,640,005 SUCCINHYDRAZIDES Waldo B. Ligett, Berkley, Rex D. Closson, Detroit, and Calvin N. Wolf, Ferndale, Mich., assignors to Ethyl Corporation, New York, N. Y., a corporation of Delaware No Drawing.

Application October 28, 1950,

Serial No. 192,806

9 Claims.

This invention relates to novel substituted succinhydrazides. In particular our invention relates to a novel class of compounds which have utility as fungitoxicants, methods of formulating such compounds into useful fungicides and methods of their application.

The compounds of our invention comprise the class of monoand disubstituted 1,2,4,5-tetrahydropyridazine-3,S-diones, and are characterized by being potent biocides, being particularly effective against fungusorganisms. Our compounds can be described by the general formula wherein the substituents X and Y are the same or different, and are selected from hydrogen, alkyl, alkenyl and negative radicals, but not more than one of X or Y is hydrogen. By alkyl group we mean straight chain, branched chain or cyclic saturated hydrocarbon radicals, while we refer to straight chain, branched chain or cyclic hydrocarbon radicals, containing one or more points of unsaturation, as alkenyl groups. Among the negative radicals which comprise certain embodiments of the novel compounds of our invention we include the halogens, the sulfhydryl group (-SH) mercaptans (-SR), the trichloromethylthio (SGC13) group, alkyland aryloxy, acyloxy and aroyloxy (RCOO), nitroso, nitro, amino, and monoand di-substituted amino.

Correct nomenclature for the compounds of our invention requires that they be referred to as derivatives of 1,2,4,5 -tetrahydropyridazine-3,6- dione, wherein one or more substituents are substituted in the 4-, or 4,5-positions, that is, at least one of the methylene groups is substituted. However, for the sake of brevity we can refer to the compounds of our invention as substituted succinhydrazides. Thus, our compounds are referred to as 4-, and LB-substituted succinhydrazides.

One method of synthesizing the substituted succinhydrazides of our invention. comprises treating hydrazine or hydrazine hydrate with. the anhydride of the appropriately substituted succinic acid. Reaction proceeds readily in most cases, and requires the use of a solvent tomoderate the exothermic reaction.

A wide variety of radicals can be substituted in the 1,2,4,5 tetrahydropyridazine 3,6 dione structureto produce novel materials. useful as fungicidal agents, and possessing wide utility as intermediates in chemical synthesis. Illustrative of these substituents are the halogens. Thus, fluorine, chlorine, bromine, or iodine can be introduced singly into the gi-position, or in pairs to the 4- and 5-positions. Likewise, in the dihalogen substituted embodiments of our compounds, we can employ two different halogens, thus forming, for example, the4-ch1oro-5-fluoro-, 4-ohloro-5-bromo-, 4-chloro-5-iodo-, 4-bromo- 5-iodo-, 4-bromo-5-fluoro-, and 4-fluoro-5-iodosuccinhydrazides.

Other useful embodiments of our novel compounds comprise those in which one or more sulfur containing groups are in the 4- or 5-, or 4,5-positions. Such sulfur containing roups include, for example the sulfhydryl group, the trichloromethylthio group, and substituted mercapto group, wherein R is alkyl, such as, for example, methyl, ethyl, propyl, n-butyl, i-butyl, amyl, 'hexyl, dodecyl, benzyl, or phenylethyl, or aryl or substituted aryl, typical examples of which are phenyl, tolyl, xylyl, and naphthyl.

Further typical examples of substituent groups which can be substituted in the 4-, 5-, or 4,5- positions of our novel compounds comprise alkyl, alkenyl, alkoxy, aryloxy and acyloxy and aroyloxy groups. Among the alkyl groups, we can substitute for example methyl, ethyl, propyl, isopropyl, butyl, and amyl groups, while the alkenyl embodiments can include such typical examples as propenyl, butenyl, sec.-butenyl, and cyclohexenyl. Typical examples of alkoxy groups which we employ comprise methoxy, ethoxy, propoxy, isopropoxy, allyloxy, 2-methylhexoxy, l3- chloroethoxy, B-aminoethoxy, and benzyloxy. As aryloxy substituents we can employ such typical groups as phenoxy, 4'-isopropylphenoxy, 2,4'- dichlorophenoxy and '3-nitrophenoxy. Among the acyloxy and aroylox groups we can employ in the 4-, 5-, or 4,5-positions of our 1,2,4,5-tetradihydropyridazine 3,6 diones, representative members include 'acetoxy, mono-, diand trichloroacetoxy, propionoxy, lauroyloxy, a-tOlllYloxy, benzoyloxy, toluyloxy, xyloloxy, anisoyloxy, anthranoyloxy; 4-chlorobenzoloxy and 2'-hydroxybenzoyloxy.

Among nitrogen containing groups which we can substitute in the 4-, 5-, or 4,5-positions of our succinhydrazides typical examples include the nitroso, nitro and amino groups. The amino groups can be unsubstituted or can comprise the monoand di-alkyl and aryl or aryl alkyl amines. Illustrative of such amine groups are methylamino, ethylamino, hexylamino, N-methyl-N- ethylamino, isopropylamino, cyclohexylamino, 2'-' methylhexylamino, B-hydroxwethylamino, anilino, N-phenyl-N-methylamino, piperidyl. morpholino, and pyridyl.

As pointed out in describing our halo-, dihaloand mixed halo-substituted compounds, the various alkyl, alkenyl and negative radicals of thecompounds of our invention can also be co-substituted in many variations and combinations on the 4-, 5-, or 4,5-positicns of our succinhydrazides.

To illustrate one method of preparing the substituted succinhydrazides of rourj invention the following examples are presented wherein all parts and percentages are by weight.

Example I 4,5-dzchlrosuccinhydrazide.--To a solution of.

solid havinga melting, point of260.to;263 C., -was 17 parts or 39 per. cent based on .thB--a;a':diGh101O- succinic anhydride. The product contained 41 per cent chlorine, while-the formula C4-II402N2C12 requires 39 .per cent chlorine.

Example II :5 aZlcenylsuccinhydrazide.-An Malkenylsuccinic anhydride (50 parts) wherein thea'lkenyl group wasa mixture of twelve to fourteen carbon atom unsaturated aliphatic radicals was dissolved in 200 parts of n-butanol. To this solution, at reflux temperature-was added, with'stirring, '10 parts of hydrazine hydratein 40 parts of ethanol. After proceeding as in the foregoing example the product, a 5-alkenylsuccinhydrazide separated as a viscous oil in"85 per cent yield. This-product was recovered by decantation.

Other substituted succinic 'anhydrides can be condensed with hydrazine hydrate according to the-procedure of the foregoing'examples to produce other succinhydrazides of our invention. Thus, for example, when each of 'a-ChIOIO-n a-chloro-a-'bromo-, a-iluoro-a'-riitro-, u-Illt-IO-n a-mercapto a-trichloromethylthio-, n-l'l'lGiEhOXY- a'F-nitro a,e'-diacetoxy-, a-anilino a" iodo, allitl'0S0a'-Ch10IO-, a-methylmercaptoa a-(N- methyl-N-butylamino) 0." nitro--, a-methyl a-chloro-d-butenyh, acyclohexy'l a'-acetoxy-, and aamino-succinic anhydride is treated in benzene or an alcohol solution with a solution of hydrazine hydrate in ethyl alcohol there is obtained, respectively, 4 chl0ro-, 4 'chloro-fibromo, 4-fiuoro-5-nitro-, 4-nitro-, 4mercapto, 4-trichloromethylthio-, 4-methoxy-5-nitro-, 4,5 diacetoxy-, 4-anilino 5 iodo, 4.-----nitroso-'5- chloro-, 4 methylmercapto-. l-"(N-methyl-Nn buty1amino)-5-nitro-, 4 meth-yl-, -4-chlo1'o-'5- butenyl-, 4-cyclohexyl -'5-acetoxy-, and 4-aminosuccinhydrazide.

The compounds of our invention can be employed as fungicides and for 'the 'prevention of the germination of the spores of fungi. To demonstrate the utility of the succinhydrazides of our invention as fungicidal compositions we determined the concentration at which the germination of 50 per cent of the spores of each of the fungi A'Ztemaria oleracea and Scle-rotinia fructicola is inhibited. -The former is responsible for the potato blight, while the latter causes peach rot. These fungi are representative of fungus types which are responsible forheavy'crop damage. The ability to control these fungi is a reliable indication of the general applicability of our fungicides to protect these and other important agricultural crops. These tests were conducted as follows: 100 parts of the active ingredi- .chloro-, ;4-butylmercapto-., nitro-, -nitmso-fiemercapto- -and-.4,5-diacetoxyent was .triturated with *1',000"parts of distilled 1 water containing one pert'o'f the commercial dispersant Triton X-100. This standard suspension .was thereupon further diluted with distilled water and. the. concentration at which one-half of the fungi contained in a drop of water on a microscope-slide were prevented from sporilating was determined. :example, under these conditions 4.5dichloro succinhydrazide was effective ata concentration as low as 10 p. p. in. When the 'followingtypical examples of the compounds 'of 'our invention are so-applied to cultures of these fungi, they are also effective at a similar low concentration: 4-'-chloro-, 4,5 dibromo-, 4-,amin0-, --,4r-,trichloromethylthiow, 4 nitr0-5- 4 methylamino-fisuccinhydrazide.

'Other'examples ofthe novel class ofcompounds which we have provided willbe apparent, those specific.examplesenumerated hereinbeing merely illustrative. .Eurthermora-other methods for their; preparation -will-.be :anparent to those skilled in theaart, and the foregoing'examplesof preparation are gpresentedmerely to illustrate one method :for their preparation.

We claim:

1. As new compositions of matter, 1, 4, 5- tetrahydropyridazine-3,6-diones in which at least one of the methylene groups is substituted with a member selected from .the class consisting oi lower alkyl, lower alkenyl and halogen radicals.

2. The composition of claim 1 in which at least one of the methylene groups is substituted with a lower alkenyl radical.

3. The z'composition-ofclaim 1 in which at least one of the .methylenegroups is substituted with a halogen radical.

4. A fungicidal'composition containing as the principal fungicidal agent the composition 01' claim 1.

5. The methodof treatingmaterials susceptible to fungus attack with a fungicidal composition containing as the principal :active ingredient the composition of claim 1.

6. The composition-of claim 1 in which at least one of the methylene groups is substituted with a lower alkyl radical.

'7. A process for the -manufacture of 1,2,4-5- tetrahydropyridazinee3;6-:dione in which at least one of the methylene groups is substituted with a member selected from the group consisting of lower ,alk-yl, lower alkenyl and halogen radicals which comprisesyreactinga member selected from the group consisting of hydrazine and hydrazine hydrate with a succinic anhydride wherein at least one of the-methylene groups of said succinic anhydride 'is substituted with a member selected from 'thegroup'consis'ting of lower alkyl, lower alkenyl and 'halogenradicals.

8. 4,5-dichlorosuccinhydrazide.

'9. Allcenyl :succinhydrazidewherein said alkenyl group contains from 1 to 14 carbon atoms.

WALDO B. LIGETI. REX D. CLOSS'ON. CALVIN N. WOLF.

References Cited in the file of this patent 'Feuer et al., J. Am. Chem. Soc. 73, 4716-4719 (1951).

Sernagiotto et al., Gazz. Chim. et a1. 44, '538 (1914).

Curtius, J. Prakt Chem. (2) 92,80 (1915).

Beilstein, Vierte Auflage. vol. 24, p. 312.

Hoffmann, Science 109, 588-590 (1949). 

1. AS NEW COMPOSITIONS OF MATTER, 1, 2, 4, 5TETRAHYDROPYRIDAZINE-3,6-DIONES INWHICH AT LEAST ONE OF THE METHYLENE GROUPS IS SUBSTITUTED WITH A MEMBER SELECTED FROM THE CLASS CONSISTING OF LOWER ALKYL, LOWER ALKENYL AND HALOGEN RADICALS.
 7. A PROCESS FOR THE MANUFACTURE OF 1,2,4-5TETRAHYDROPYRIDAZINE-3,6-DIONE IN WHICH AT LEAST ONE OF THE METHYLENE GROUPS IS SUBSTITUTED WITH A MEMBER SELECTED FROM THE GROUP CONSISTING OF LOWER ALKYL, LOWER ALKENYL AND HALOGEN RADICALS WHICH COMPRISES REACTING A MEMBER SELECTED FROM THE GROUP CONSISTING OF HYDRAZINE AND HYDRAZINE HYDRATE WITH A SUCCINIC ANHYDRIDE WHEREIN AT LEAST ONE OF THE METHYLENE GROUPS OF SAID SUCCINIC ANHYDRIDE IS SUBSTITUTED WITH A MEMBER SELECTED FROM THE GROUP CONSISTING OF LOWER ALKYL, LOWER ALKENYL AND HALOGEN RADICALS. 